Research advances in new technologies in targeted protein degradation / 药学学报

In recent years, the targeted protein degradation technology has developed quickly, with proteolysis-targeting chimera (PROTAC) as the best-known strategy through exploring the ubiquitin-proteasome system. A number of new targeted protein degradation strategies have been emerging to expand the scope of protein degradation technology, including lysosome-targeting chimeras (LYTACs), autophagy-targeting chimeras (AUTACs), autophagosome-tethering compounds (ATTECs) and chimeras based on chaperone-mediated autophagy (CMA). The emerging methodologies have explored another important protein degradation system in eukaryotes-lysosomal systems, such as the endosome-lysosome pathway and the autophagy-lysosome pathway. This review summaries the mechanisms and features of different strategies for targeted protein degradation, with a special emphasis on the new targeted protein degradation technologies, such as their current status, advantages and limitations.

Application of computed tomography virtual noncontrast spectral imaging in evaluation of hepatic metastases: a preliminary study / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>The objective was to qualitatively and quantitatively evaluate hepatic metastases using computed tomography (CT) virtual noncontrast (VNC) spectral imaging in a retrospective analysis.</p><p><b>METHODS</b>Forty hepatic metastases patients underwent CT scans including the conventional true noncontrast (TNC) and the tri-phasic contrast-enhanced dual energy spectral scans in the hepatic arterial, portal venous, and equilibrium phases. The tri-phasic spectral CT images were used to obtain three groups of VNC images including in the arterial (VNCa), venous (VNCv), and equilibrium (VNCe) phase by the material decomposition process using water and iodine as a base material pair. The image quality and the contrast-to-noise ratio (CNR) of metastasis of the four groups were compared with ANOVA analysis. The metastasis detection rates with the four nonenhanced image groups were calculated and compared using the Chi-square test.</p><p><b>RESULTS</b>There were no significant differences in image quality among TNC, VNCa and VNCv images (P > 0.05). The quality of VNCe images was significantly worse than that of other three groups (P < 0.05). The mean CNR of metastasis in the TNC and VNCs images was 1.86, 2.42, 1.92, and 1.94, respectively; the mean CNR of metastasis in VNCa images was significantly higher than that in other three groups (P < 0.05), while no statistically significant difference was observed among VNCv, VNCe and TNC images (P > 0.05). The metastasis detection rate of the four nonenhanced groups with no statistically significant difference (P > 0.05).</p><p><b>CONCLUSIONS</b>The quality of VNCa and VNCv images is identical to that of TNC images, and the metastasis detection rate in VNC images is similar to that in TNC images. VNC images obtained from arterial phase show metastases more clearly. Thus, VNCa imaging may be a surrogate to TNC imaging in hepatic metastasis diagnosis.</p>

The clinical application studies of CT spinal angiography with 64-detector row spiral CT in diagnosing spinal vascular malformations.

BACKGROUND AND PURPOSE: To explore the value of CT spinal angiography with 64-detector row spiral CT in diagnosing spinal vascular malformations. METHODS: Seventeen patients with initial MR and clinical findings suggestive of spinal vascular diseases underwent CT spinal angiography. Among these, 14 patients took DSA examination within 1 week after CT scan, 7 patients underwent surgical treatment, and 6 patients underwent vascular intervention embolotheraphy. CT protocol: TOSHIBA Aquilion 64 Slice CT scanner, 0.5mm thickness, 0.5s/r, 120 kV and 350 mA, positioned at the aortic arch level, and applied with "sure start" technique with CT threshold of 180 Hu. Contrast agent Iohexol (370 mg I/ml) was injected at 6 ml/s velocity with total volume of 80 ml. The post-processing procedures included MPR, CPR, MIP, VR, etc. Among the 17 patients, four patients underwent fast dynamic contrast-enhanced 3D MR angiography imaging. CT spinal angiography and three-dimensional contrast-enhanced MR angiography (3D CE-MRA) images were compared and evaluated with DSA and operation results based on disease type, lesion range, feeding arteries, fistulas, draining veins of vascular malformation by three experienced neuroradiologists independently, using double blind method. The data were analyzed using SPSS analytic software with chi(2)-test. We compared the results with DSA and operation results. RESULTS: The statistical analysis of the diagnostic results by the three experienced neuroradiologists had no statistical difference (P>0.05). All of the 17 patients showed clearly the abnormality of spinal cord vessels and the range of lesions by CT spinal angiography. Among them, one patient was diagnosed as arteriovenous fistulas (AVF) by MRI and CT spinal angiography, which was verified by surgical operation. DSA of the same patient, however, did not visualize the lesion. One case was diagnosed as AVM complicated with AVF by DSA, but CT spinal angiography could only show AVM not AVF. The type differentiations of all the other 16 patients were consistent with DSA results. For 13 cases with positive CT spinal angiography results, DSA displayed 20 feeding vessels, among which 16 vessels were displayed correctly by CT spinal angiography, four could not be visualized, and two turned out to be false-positive. Fistulas were not displayed in six cases by CT spinal angiography. Draining veins were displayed clearly in all cases, which agreed with DSA results. Four cases who took CE-MRA obtained the same type diagnosis as that from CT spinal angiography. Feeding arteries were not displayed in CE-MRA of one case, but could be clearly visualized in other three cases, and the results agreed with CTA and DSA results. Fistulas could be seen in two cases. Draining veins and the disease range could be displayed distinctly by 3D CE-MRA. CONCLUSION: CT spinal angiography is quite valuable for diagnosing vascular malformation of spinal cord. It can be a screening exam before DSA, and has a guiding effect on DSA, reducing the amount of time required for DSA.

The initial clinical application of multi-detector CT on spinal angiography / 中华放射学杂志

Objective To explore the value of Multi-detector CT in spinal cord angiography. Methods Ten patients with initial MR and clinical findings suggestive of spinal cord vessel disease were performed CT spinal cord angiography.Among these,7 patients were performed DSA later within 1 week, and 4 patients were therapy by operation.CT protocol:Toshiba Aquilion 64 slice CT scanner,0.5 mm thickness,0.5/r,120 kV,350 mA,choose aortic arch level as inspection position,and use"surestart" technique with CT threshold 180 HU.Contrast medium was Iohexol(370 mg I/ml),with injection velocity of 6 ml/s.The total volume was 80 ml.The CT spinal cord angiography images were analyzed according to disease model,disease range,feeding artery,fistula,draining veins,and were compared with DSA and operation results.Results All CT spinal cord angiography images displayed spinal vessel malformation. Among these,3 patients were inner-medullary arteriovenous malformation;2 patients were peri-medullary arteriovenous fistula;5 patients were spinal dural arteriovenous fistula.All cases showed disease range,and draining veins clearly,one patient had two vessels that were false positive,and all the other cases showed feeding arteries clearly,which were confirmed by DSA.Conclusion There are great values for CT spinal angiography in diagnosing spinal vessel disease,it can be a screening exam before DSA.